Drug interactions with tissue receptors are believed to be highly specific and pharmacologically active substances exert their biological effects by interacting with these tissue receptors. Another very specific interaction is the immune reaction. The interaction of antibodies with a protein antigen is a very complex one as each antigenic molecule has many determinant groups with which the antibody can bind. Drugs, because of their low molecular weight, do not generally yield antibodies but they can be made to act as haptenic moieties when conjugated to carrier proteins. Some of the antibodies thus generated recognize various parts of the haptenic group. Thus, it should be possible to develop antibodies which have a confirmational complementarity to a drug very much like the receptor. The antibodies could then be used to bind the endogenous ligand for the receptor.
There is considerable evidence which suggests that the analgesic effects produced by the opiates are mediated via discrete functional receptors. This evidence includes the rigid steric requirements necessary for analgesic activity, the ability of naloxone to to antagonize the pain suppressant effects of all the structurally diverse opiates, recent demonstration of the presence in nervous tissue of saturatable, high affinity stereospecific binding sites for opiates which can be blocked by naloxone, and of a peptide with morphine-like properties.
It is thus reasonable to assume that any substance with morphine-like biological properties should bear, to at least some extent, structural similarities to morphine. In order for the molecule to elicit an effect, it must first bind or interact with the receptor. Thus, there is a recognition by the receptor of the agonist. Antibodies have previously been disclosed (Spector and Parker, Science, 168, 1347 [1970]) toward the haptenic molecule morphine by conjugating it to the protein carrier bovine serum albumin (BSA). The antibodies produced by this immunogen recognize various determinant portions of the morphine molecule specifically (Spector, J. Pharmacol. Exp. Ther. 178, No. 2, 253 [1970]).